Shift in bile acid metabolizing microbial enzymes during gastrointestinal inflammation

Microbial metabolites including bile acids (BAs) shape gastrointestinal homeostasis and are altered in inflammatory bowel diseases, suggesting a potential role in disease etiology. Host-derived BAs are converted into microbe-derived BAs via C7alpha-dehydroxylation carried out by bai operon gene products found in strictly anaerobic commensals such as Clostridium scindens and CAG-103 (Firmicutes). Hydroxyl groups can also be epimerized at the C3 and C7 positions via hydroxysteroid dehydrogenases (HSDHs) present in few select bacteria such as Ruminococcus gnavus (3a/b-HSDH,7b-HSDH) and Escherichia coli (7a-HSDH). Recently, we discovered that endoscopically visible mucosal biofilms in inflammatory bowel disease patients are accompanied by increased fecal excretion of host-derived BA (Baumgartner et al., 2021. Gastroenterology), including host-derived isoBA species normally found at low levels in healthy subjects. We aim to perform a comprehensive analysis of microbial BA converting enzymes in various ‘omics datasets. BA converting enzymes will then be correlated to fecal BA levels as determined via metabolomics, clinical phenotype, gut-liver feeback as well as immune-phenotype as assessed via plasma metabolites and gene expression. The Lifelines-DEEP and 1000 Inflammatory Bowel Disease datasets would supplement our own in-house datasets.